U.S. patent application number 10/143442 was filed with the patent office on 2003-11-13 for physiological sample collection devices and methods of using the same.
Invention is credited to Leong, Koon-Wah, McAllister, Devin, Olson, Lorin, Teodorczyk, Maria, Yuzhakov, Vadim.
Application Number | 20030212344 10/143442 |
Document ID | / |
Family ID | 29249855 |
Filed Date | 2003-11-13 |
United States Patent
Application |
20030212344 |
Kind Code |
A1 |
Yuzhakov, Vadim ; et
al. |
November 13, 2003 |
Physiological sample collection devices and methods of using the
same
Abstract
Devices, systems and methods are provided for piercing the skin,
accessing and collecting physiological sample therein, and
measuring a characteristic, e.g., an analyte concentration, of the
sampled physiological sample. The subject devices are in the form
of a test strip that include a biosensor and at least one
skin-piercing element affixed to the test strip. The skin-piercing
element conveys a biological fluid sample to a sensor element in
the test strip. Systems are provided which include one or more test
strip devices and a meter for making analyte concentration
measurements. Methods for manufacturing and using the devices and
systems are also provided.
Inventors: |
Yuzhakov, Vadim; (San Jose,
CA) ; McAllister, Devin; (San Jose, CA) ;
Olson, Lorin; (Scotts Valley, CA) ; Leong,
Koon-Wah; (Sunnyvale, CA) ; Teodorczyk, Maria;
(San Jose, CA) |
Correspondence
Address: |
BOZICEVIC, FIELD & FRANCIS LLP
200 MIDDLEFIELD RD
SUITE 200
MENLO PARK
CA
94025
US
|
Family ID: |
29249855 |
Appl. No.: |
10/143442 |
Filed: |
May 9, 2002 |
Current U.S.
Class: |
600/583 |
Current CPC
Class: |
A61B 5/150213 20130101;
A61B 5/150954 20130101; A61B 5/157 20130101; A61B 5/150068
20130101; A61B 5/150022 20130101; A61B 5/15178 20130101; A61B
5/150435 20130101; A61B 5/150419 20130101; A61B 5/15194 20130101;
A61B 5/150358 20130101; A61B 5/15117 20130101; A61B 5/150824
20130101; A61B 5/15113 20130101; A61B 5/1519 20130101 |
Class at
Publication: |
600/583 |
International
Class: |
A61B 005/00 |
Claims
1. A lance element for attachment to a test strip to access body
fluid and convey it to a test strip sensor, said lance comprising:
a substantially planar base; a piercing element comprising an
opening occupying a substantial portion of a width, diameter or
length dimension of said piercing element; and a fluid pathway in
communication with said opening, wherein a pooling area is created
within the skin by said opening upon insertion of said piercing
element into the skin of a subject.
2. The lance element of claim 1, wherein said opening has a volume
in the range from about 50 to 500 nL.
3. The lance element of claim 1, wherein said opening occupies from
about 50% to 95% of the volume occupied by said piercing
element.
4. The lance element of claim 1, comprising a plastic material.
5. The lance element of claim 1, wherein said fluid pathway is
dimensioned to apply a capillary force on fluid present within said
pooling area.
6. The lance element of claim 1, further comprising a recess within
a surface of said base, wherein said recess is in fluid
communication with said opening.
7. A lance element for attachment to a test strip to access body
fluid and convey it to a test strip sensor, said lance comprising:
a substantially planar base and a piercing element, wherein a fluid
pathway is provided from said piercing element into said base.
8. A lance element for attachment to a test strip to access body
fluid and convey it to a test strip sensor, said lance comprising:
a substantially planar base and a piercing element comprising an
opening occupying a substantial portion of a width, diameter or
length dimension of said piercing element.
9. A test strip combination comprising: a complete test strip
comprising biosensor and a support member; a separate lance element
attached to said test strip, said lance element comprising at least
one piercing element and being adapted to convey a fluid sample
obtained by said piercing element to said biosensor.
10. The test strip combination of claim 9, wherein said test strip
has an electrochemical configuration.
11. The test strip combination of claim 9, wherein said test strip
has a photometric or colorimetric configuration.
12. The test strip combination of claim 9, wherein said lance
element comprises a metal material.
13. The test strip combination of claim 9, wherein said lance
element comprises a plastic material.
14. The test strip combination of claim 9, wherein said lance
element is selected from a group consisting of those described in
claim 1, claim 7 and claim 8.
15. The test strip combination of claim 9, wherein said lance
element comprises a substantially planar base, said base attached
to said test strip by adhesive.
16. The test strip combination of claim 9, wherein said lance
element comprises a substantially planar base and opposing hooks
positioned to attach said lance element to said test strip.
17. A system for determining the concentration of at least one
analyte in a physiological sample, said system comprising: at least
one test strip combination according to claim 9, and a meter for
automatically determining the concentration of analyte in the
physiological sample, wherein said meter is configured for
receiving said test strip device.
18. The system of claim 16, wherein said lance element is selected
from a group consisting of those described in claim 1, claim 7 and
claim 8.
19. A method for determining the concentration of at least one
analyte within a physiological fluid sample, said method
comprising: providing the system of claim 18 wherein said test
strip combination is operatively received within a distal end of
said meter; spring-loading said test strip combination within said
meter; operatively contacting said distal end of said meter with a
targeted skin surface; releasing the spring-loaded test strip
combination, wherein said targeted skin surface is pierced by said
piercing element; and collecting sample and applying it to said
biosensor.
20. The method to claim 19, further comprising: applying pressure
against said target skin surface with said distal end of said
meter.
21. The method of claim 20, wherein said of applying optimal
pressure comprises the steps of: sensing the pressure applied;
indicating the amount of said sensed pressure; and adjusting said
applied pressure if necessary according to said indicated amount of
pressure.
22. A method of producing a tester, the method comprising:
providing a lance element as described in claim 1, providing a test
strip having a substrate and biosensor; and attaching said lance
element base to said test strip.
23. The method of claim 22, wherein said attaching is accomplished
at said sensor.
24. The method of claim 22, wherein said attaching is accomplished
along said support.
25. The method of claim 22, wherein said attaching is accomplished
with at least one clip.
26. The method of claim 22, wherein said attaching is accomplished
with adhesive.
Description
FIELD OF THE INVENTION
[0001] The invention relates to the collection of physiological
samples and the determination of analyte concentrations
therein.
BACKGROUND OF THE INVENTION
[0002] Analyte concentration determination in physiological samples
is of ever increasing importance to today's society. Such assays
find use in a variety of application settings, including clinical
laboratory testing, home testing, etc., where the results of such
testing play a prominent role in the diagnosis and management of a
variety of disease conditions. Analytes of interest include glucose
for diabetes management, cholesterol for monitoring cardiovascular
conditions, and the like. In response to this growing importance of
analyte concentration determination, a variety of analyte
concentration determination protocols and devices for both clinical
and home testing have been developed.
[0003] In determining the concentration of an analyte in a
physiological sample, a physiological sample must first be
obtained. Obtaining the sample often involves cumbersome and
complicated devices which may not be easy to use or may be costly
to manufacture. Furthermore, the procedure for obtaining the sample
may be painful. For example, pain is often associated with the size
of the needle used to obtain the physiological sample and the depth
to which the needle is inserted. Depending on the analyte and the
type of test employed, a relatively large, single needle or the
like is often used to extract the requisite amount of sample.
[0004] The analyte concentration determination process may also
involve a multitude of steps. First, a sample is accessed by use of
a skin-piercing mechanism, e.g., a needle or lancet, which
accessing may also involve the use of a sample collection
mechanism, e.g., a capillary tube. Next, the sample must then be
transferred to a testing device, e.g., a test strip or the like,
and then oftentimes the test strip is then transferred to a
measuring device such as a meter. Thus, the steps of accessing the
sample, collecting the sample, transferring the sample to a
biosensor, and measuring the analyte concentration in the sample
are often performed as separate, consecutive steps with various
device and instrumentation.
[0005] Because of these disadvantages, it is not uncommon for
patients who require frequent monitoring of an analyte to simply
become non-compliant in monitoring themselves. With diabetics, for
example, the failure to measure their glucose level on a prescribed
basis results in a lack of information necessary to properly
control the level of glucose. Uncontrolled glucose levels can be
very dangerous and even life threatening.
[0006] Attempts have been made to combine a lancing-type device
with various other components involved in the analyte concentration
determination procedure in order to simplify the assay process. For
example, U.S. Pat. No. 6,099,484 discloses a sampling device which
includes a single needle associated with a spring mechanism, a
capillary tube associated with a pusher, and a test strip. An
analyzer may also be mounted in the device for analyzing the
sample. Accordingly, the single needle is displaced toward the skin
surface by un-cocking a spring and then retracting it by another
spring. A pusher is then displaced to push the capillary tube in
communication with a sample and the pusher is then released and the
fluid is transferred to a test strip.
[0007] U.S. Pat. No. 5,820,570 discloses an apparatus which
includes a base having a hollow needle and a cover having a
membrane, whereby the base and cover are connected together at a
hinge point. When in a closed position, the needle is in
communication with the membrane and fluid can be drawn up through
the needle and placed on the membrane of the cover.
[0008] There are certain drawbacks associated with each of the
above devices and techniques. For example, the devices disclosed in
the aforementioned patents are complex, thus decreasing ease-of-use
and increasing manufacturing costs. Furthermore, as described, a
single needle design may be associated with increased pain because
the single needle must be large enough to extract the requisite
sample size. Still further, in regards to the '484 patent, the
steps of activating and retracting a needle and then activating and
retracting a capillary tube adds still more user interaction and
decreases ease-of-use.
[0009] As such, there is continued interest in the development of
new devices and methods for use in the determination of analyte
concentrations in a physiological sample. Of particular interest
would be the development of integrated devices, and methods of use
thereof, that are efficient, involve minimal pain, are simple to
use and which may be used with various analyte concentration
determination systems. However, in producing such devices the
present invention places particular emphasis on issues associated
with manufacturing and distribution, thereby offering more cost
effective and flexible options, both to consumers and
manufactures.
SUMMARY OF THE INVENTION
[0010] Devices, systems and methods are provided for piercing the
skin, accessing and collecting physiological sample therein, and
measuring a characteristic of the physiological sample. The subject
devices include at least one microneedle or skin-piercing element
affixable to a test strip. The subject test strips include a
biosensor, wherein the at least one skin-piercing element is
separately attached to the biosensor.
[0011] Preferred skin-piercing elements have a space-defining
configuration in which, upon insertion into the skin, creates a
space or volume within the pierced tissue. This space serves as a
reservoir or pooling area within which bodily fluid is caused to
pool while the skin-piercing element is in situ. A capillary
channel or fluid pathway extending from the pooling space to within
the test strip transfers pooled fluid present within the pooling
space to the biosensor. In certain embodiments, the space-defining
configuration is a recess within a surface of the skin-piercing
element. Such a recess may have a concave configuration. In other
embodiments, the space-defining configuration is an opening which
extends transverse to a dimension of the skin-piercing element and
occupies a substantial portion of a width or diameter dimension as
well as a substantial portion of a length dimension of the
microneedle.
[0012] Generally, test strips used in connection with the needle or
lance members of the present inventions may include electrochemical
or photometric/colorimetric sensors. Other types of test strips may
be used as well.
[0013] Needles or lance members according to the present invention
may be affixed to test strips members in a number of ways. They may
be affixed directly, e.g., using adhesive, chemical or ultrasonic
welding. Alternately, mechanical attachment via clips hasps or the
like may be employed.
[0014] Numerous advantages are presented in so-producing completed
test strips/lances member combinations.
[0015] The subject systems include one or more subject test strip
devices and a meter for receiving a subject test strip and for
determining a characteristic of the sampled fluid, e.g., the
concentration of at least one analyte in the sample, collected by
within the test strip's biosensor. Moreover, such a meter may also
provide means for activating and manipulating the test strip
wherein the skin-piercing structure is caused to pierce the skin.
Additionally, the meter may provide means for storing one or more
subject test strips, or a cartridge containing a plurality of such
test strips.
[0016] Also provided are methods for using the subject devices, as
well as kits that include the subject devices and/or systems for
use in practicing the subject methods. The subject devices, systems
and methods are particularly suited for collecting physiological
sample and determining analyte concentrations therein and, more
particularly, glucose concentrations in blood, blood fractions or
interstitial fluid. The present invention further includes methods
for fabricating the subject test strip devices, in which a
microneedle or skin-piercing element is affixed to a
complete/discrete test strip unit. The subject fabrication methods
may be used to fabricate individual test strip devices or a
plurality of such test strip devices on a web, film or sheet of
suitable material.
[0017] These and other objects, advantages, and features of the
invention will become apparent to those persons skilled in the art
upon reading the details of the methods and systems of the present
invention which are more fully described below.
BRIEF DESCRIPTION OF THE DRAWINGS
[0018] Each of the following figures diagrammatically illustrate
aspects of the present invention. Variation of the invention from
that shown in the figures is contemplated.
[0019] FIG. 1 is a perspective view of a representative meter as
may be used in connection with variations of the present
invention.
[0020] FIGS. 2A and 3A are perspective views of the invention as
used in calorimetric test devices; FIGS. 2B and 3B are perspective
views of lance members to be attached to test strips by adhesive
and mechanical fasteners.
[0021] FIGS. 4A and 4B are perspective hidden-line views of the
invention as used in electrochemical test devices, wherein plastic
and metal lance member are shown.
[0022] FIGS. 5A is an exploded perspective view of an alternate
lance configuration employing dispersion channels; FIG. 5B is a
perspective view of the components in FIG. 4A shown assembled from
below.
[0023] FIG. 6 is a perspective view of an alternate lance member
resembling that in FIGS. 5A and 5B, but provided in a low-profile
format.
[0024] FIG. 7 is a perspective view of yet another lance member,
this one employing an inset dispersion zone.
DETAILED DESCRIPTION OF THE INVENTION
[0025] In describing the invention in greater detail than provided
in the Summary above, colorimetric and electrochemical test strips
sensors are first described, followed by discussion of features and
the use of exemplary combination test strip meter and lancing
device of the present invention. Then, the manner in which
colorimetric and electrochemical test strip may be provided in
connection with examples of the present invention is set forth.
This description is followed by disclosure of various alternate
lance/needle member configurations. Then, methods of manufacture
and kits advantageously incorporating components of the present
invention are described.
[0026] Before the present invention is described in such detail,
however, it is to be understood that this invention is not limited
to particular variations set forth and may, of course, vary.
Various changes may be made to the invention described and
equivalents may be substituted without departing from the true
spirit and scope of the invention. In addition, many modifications
may be made to adapt a particular situation, material, composition
of matter, process, process act(s) or step(s), to the objective(s),
spirit or scope of the present invention. All such modifications
are intended to be within the scope of the claims made herein. For
example, description of the use of electrochemical and photometric
sensor type test strips is not intended to be limiting; those
skilled in the art will appreciate that the subject devices,
systems and methods are useful in the measurement of other physical
and chemical characteristics of biological substances, e.g., blood
coagulation time, blood cholesterol level, etc.
[0027] Methods recited herein may be carried out in any order of
the recited events which is logically possible, as well as the
recited order of events. Furthermore, where a range of values is
provided, it is understood that every intervening value, between
the upper and lower limit of that range and any other stated or
intervening value in that stated range is encompassed within the
invention. Also, it is contemplated that any optional feature of
the inventive variations described may be set forth and claimed
independently, or in combination with any one or more of the
features described herein.
[0028] All existing subject matter mentioned herein (e.g.,
publications, patents, patent applications and hardware) is
incorporated by reference herein in its entirety except insofar as
the subject matter may conflict with that of the present invention
(in which case what is present herein shall prevail). The
referenced items are provided solely for their disclosure prior to
the filing date of the present application. Nothing herein is to be
construed as an admission that the present invention is not
entitled to antedate such material by virtue of prior
invention.
[0029] Reference to a singular item, includes the possibility that
there are plural of the same items present. More specifically, as
used herein and in the appended claims, the singular forms "a,"
"and," "said" and "the" include plural referents unless the context
clearly dictates otherwise. It is further noted that the claims may
be drafted to exclude any optional element. As such, this statement
is intended to serve as antecedent basis for use of such exclusive
terminology as "solely," "only" and the like in connection with the
recitation of claim elements, or use of a "negative" limitation.
Finally, it is noted that unless defined otherwise herein, all
technical and scientific terms used herein have the same meaning as
commonly understood by one of ordinary skill in the art to which
this invention belongs.
[0030] Colorimetric/Photometric Sensor Variations
[0031] In testers including calorimetric or photometric (herein
used interchangeably) biosensor, the same is provided by at least a
matrix and/or a membrane for receiving a sample and a reagent
composition (set within the matrix or membrane) set upon a support
structure. Where a membrane as well as a matrix is provided, the
membrane will generally be placed opposite of the support structure
upon the matrix. A membrane advantageously includes apertures or
pores for sample access.
[0032] In some embodiments, the sensor comprises a membrane
containing a reagent composition impregnated therein while a matrix
may or may not contain reagent composition. Often the matrix
preferably provides a deposition area for the various members of
the signal producing system, described infra, as well as for the
light absorbing or chromogenic product produced by the signal
producing system, i.e., the indicator, as well as provides a
location for the detection of the light-absorbing product produced
by the indicator of the signal producing system.
[0033] A membrane provided may comprise a membrane that exhibits
aqueous fluid flow properties and is sufficiently porous (i.e.,
provides sufficient void space) for chemical reactions of a signal
producing system to take place. Ideally, the membrane pore
structure would not support red blood cell flow to the surface of
the membrane being interrogated (i.e., the color intensity of which
is a subject of the measurement correlated to analyte
concentration). Any matrix provided may or may not have pores
and/or a porosity gradient, e.g. with larger pores near or at the
sample application region and smaller pores at the detection
region.
[0034] Materials from which a membrane may be fabricated vary,
include polymers, e.g. polysulfone, polyamides, cellulose or
absorbent paper, and the like, where the material may or may not be
functionalized to provide for covalent or non-covalent attachment
of the various members of the signal producing system. In a tester
made a thin membrane material, the tester may require less than 1/2
.mu.l of sample to wet a sufficiently large area of the membrane to
obtain a good optical measurement.
[0035] Regarding suitable matrices, a number of different types
have been developed for use in various analyte detection assays,
which matrices may differ in terms of materials, dimensions and the
like, where representative matrices include, but are not limited
to, those described in U.S. Pat. Nos.: 4,734,360; 4,900,666;
4,935,346; 5,059,394; 5,304,468; 5,306,623; 5,418,142; 5,426,032;
5,515,170; 5,526,120; 5,563,042; 5,620,863; 5,753,429; 5,573,452;
5,780,304; 5,789,255; 5,843,691; 5,846,486; 5,968,836 and
5,972,294; the disclosures of which are herein incorporated by
reference.
[0036] However configured, one or more members of a signal
producing system of the biosensor produce a detectable product in
response to the presence of analyte, which detectable product can
be used to derive the amount of analyte present in the assayed
sample. In the subject test strips, the one or more members of the
signal producing system are preferably associated with (e.g.,
covalently or non-covalently attached to) at least a portion of
(i.e., the detection region) the matrix or membrane, and in many
embodiments to substantially all of the same.
[0037] The signal producing system may comprise an analyte
oxidation signal producing system. By analyte oxidation signal
producing system, it is meant that in generating the detectable
signal from which the analyte concentration in the sample is
derived, the analyte is oxidized by a suitable enzyme to produce an
oxidized form of the analyte and a corresponding or proportional
amount of hydrogen peroxide. The hydrogen peroxide is then
employed, in turn, to generate the detectable product from one or
more indicator compounds, where the amount of detectable product
generated by the signal measuring system, i.e. the signal, is then
related to the amount of analyte in the initial sample. As such,
the analyte oxidation signal producing systems present in the
subject test strips are also correctly characterized as hydrogen
peroxide based signal producing systems.
[0038] Hydrogen peroxide based signal producing systems include an
enzyme that oxidizes the analyte and produces a corresponding
amount of hydrogen peroxide, where by corresponding amount is meant
that the amount of hydrogen peroxide that is produced is
proportional to the amount of analyte present in the sample. The
specific nature of this first enzyme necessarily depends on the
nature of the analyte being assayed but is generally an oxidase or
dehydrogenase. As such, the first enzyme may be: glucose oxidase
(where the analyte is glucose), or glucose dehydrogenase either
using NAD or PQQ as cofactor; cholesterol oxidase (where the
analyte is cholesterol); alcohol oxidase (where the analyte is
alcohol); lactate oxidase (where the analyte is lactate) and the
like. Other oxidizing enzymes for use with these and other analytes
of interest are known to those skilled in the art and may also be
employed. In those preferred embodiments where the reagent test
strip is designed for the detection of glucose concentration, the
first enzyme is glucose oxidase. The glucose oxidase may be
obtained from any convenient source (e.g. a naturally occurring
source such as Aspergillus niger or Penicillum, or recombinantly
produced).
[0039] The second enzyme of such a signal producing system is an
enzyme that catalyzes the conversion of one or more indicator
compounds into a detectable product in the presence of hydrogen
peroxide, where the amount of detectable product that is produced
by this reaction is proportional to the amount of hydrogen peroxide
that is present. This second enzyme is generally a peroxidase,
where suitable peroxidases include: horseradish peroxidase (HRP),
soy peroxidase, recombinantly produced peroxidase and synthetic
analogs having peroxidative activity and the like. See, e.g., Y.
Ci, F. Wang; Analytica Chimica Acta, 233 (1990), 299-302.
[0040] Indicator compound or compounds provided are preferably ones
that are either formed or decomposed by the hydrogen peroxide in
the presence of the peroxidase to produce an indicator dye that
absorbs light in a predetermined wavelength range. Preferably the
indicator dye absorbs strongly at a wavelength different from that
at which the sample or the testing reagent absorbs strongly. The
oxidized form of the indicator may be a colored, faintly-colored,
or colorless final product that evidences a change in color of the
testing side of the membrane. That is to say, the testing reagent
can indicate the presence of glucose in a sample by a colored area
being bleached or, alternatively, by a colorless area developing
color.
[0041] Indicator compounds that are useful in the present invention
include both one- and two-component chromogenic substrates.
One-component systems include aromatic amines, aromatic alcohols,
azines, and benzidines, such as tetramethyl benzidine-HCl. Suitable
two-component systems include those in which one component is MBTH,
an MBTH derivative (see e.g., those disclosed in U.S. patent
application Ser. No. 08/302,575), or 4-aminoantipyrine and the
other component is an aromatic amine, aromatic alcohol, conjugated
amine, conjugated alcohol or aromatic or aliphatic aldehyde.
Exemplary two-component systems are 3-methyl-2-benzothiazolinone
hydrazone hydrochloride (MBTH) combined with 3-dimethylaminobenzoic
acid (DMAB); MBTH combined with
3,5-dichloro-2-hydroxybenzene-sulfonic acid (DCHBS); and
3-methyl-2-benzothiazolinone hydrazone N-sulfonyl benzenesulfonate
monosodium (MBTHSB) combined with 8-anilino-1 naphthalene sulfonic
acid ammonium (ANS). In certain embodiments, the dye couple
MBTHSB-ANS is preferred.
[0042] In yet other embodiments of colorimetric sensors that may be
used in the present invention, signal producing systems that form a
fluorescent detectable product (or detectable non-fluorescent
substance, e.g. in a fluorescent background) may be employed, such
as those described in Kiyoshi Zaitsu, Yosuke Ohkura, New
fluorogenic substrates for Horseradish Peroxidase: rapid and
sensitive assay for hydrogen peroxide and the Peroxidase,
Analytical Biochemistry (1980) 109, 109-113. Examples of such
calorimetric reagent test strips suitable for use with the subject
invention include those described in U.S. Pat. Nos. 5,563,042;
5,753,452; 5,789,255, herein incorporated by reference.
[0043] Electrochemical Sensor Variations
[0044] Instead of using a calorimetric sensor as described above,
the present invention may employ an electrochemical sensor.
Typically, an electrochemical sensor comprises at least a pair of
opposing electrodes, although electrochemical test strips with
planar electrodes may be used in the present invention.
[0045] Where opposing-electrode type strips are employed, at least
the surfaces of electrodes facing each other are comprised of a
conductive layer such as a metal, where metals of interest include
palladium, gold, platinum, silver, iridium, stainless steel and the
like as well as carbon (conductive carbon ink) and indium doped tin
oxide.
[0046] One conductive layer is preferably formed by sputtering a
thin layer of gold (Au), the other by sputtering a thin layer of
palladium (Pd). Alternately, the electrodes may be formed by screen
printing a selected conductive pattern, including conductive leads,
with a carbon or metal ink on the backing surfaces. An additional
insulating layer may be printed on top of this conductive layer
which exposes a precisely defined pattern of electrodes. However
formed, after deposition of conductive layers, the surface may be
subsequently treated with a hydrophilic agent to facilitate
transport of a fluid sample into the reaction zone there between.
Depending on the voltage sequence applied to the cell, one
electrode may serve as a counter/reference electrode and the other
as the working electrode of the electrochemical cell. However,
where a double pulse voltage waveform is employed, each electrode
acts as a counter/reference and working electrode once during
analyte concentration measurement.
[0047] Regardless of reaction zone or electrode configuration, a
reagent coating is typically provided therein. Reagent systems of
interest typically include an enzyme and a redox active component
(mediator). The redox component of the reagent composition, when
present, is made up of one or more redox agents. A variety of
different redox agents (i.e., mediators) are known in the art and
include: ferricyanide, phenazine ethosulphate, phenazine
methosulfate, pheylenediamine, 1-methoxy-phenazine methosulfate,
2,6-dimethyl-1,4-benzoquinone, 2,5-dichloro-1,4-benzoquinone,
ferrocene derivatives, osmium bipyridyl complexes, ruthenium
complexes, and the like. In many embodiments, the redox active
component of particular interest is ferricyanide, and the like. The
enzyme of choice may vary depending on the analyte concentration
which is to be measured. For example, suitable enzymes for the
assay of glucose in whole blood include glucose oxidase or
dehydrogenase (NAD or PQQ based). Suitable enzymes for the assay of
cholesterol in whole blood include cholesterol oxidase and
esterase.
[0048] Other reagents that may be present in the reaction area
include buffering agents (e.g., citraconate, citrate, malic,
maleic, phosphate, "Good" buffers and the like); divalent cations
(e.g., calcium chloride, and magnesium chloride); surfactants
(e.g., Triton, Macol, Tetronic, Silwet, Zonyl, Aerosol, Geropon,
Chaps, and Pluronic); and stabilizing agents (e.g., albumin,
sucrose, trehalose, mannitol and lactose).
[0049] Examples of electrochemical biosensors suitable for use with
the subject invention include those described in co-pending U.S.
application Ser. Nos. 09/333,793; 09/497,304; 09/497,269;
09/736,788 and 09/746,116, the disclosures of which are herein
incorporated by reference.
[0050] Test Strip Systems and Use
[0051] As mentioned above, the subject devices may be used in the
context of a subject system, which generally includes a system
capable of obtaining a physiological sample and determining a
property of the sample, where determining the property of interest
may be accomplished automatically by an automated device, e.g., a
meter. The subject system is more particularly described herein in
the context of analyte concentration determination. However, kits
or systems according to the present invention include at least one
subject test strip device 2, oftentimes a plurality of test strip
devices, where the at least one test strip device comprises at
least on skin-piercing element 4. The kits may also include a
reusable or disposable meter 6 that may be used with disposable
tests strip devices. Further, test strip kits may include a control
solution or standard (e.g., a glucose control solution that
contains a standardized concentration of glucose). A kit may also
include instructions for using test strips according to the
invention in the determination of an analyte concentration in a
physiological sample. These instructions may be present on one or
more of container(s), packaging, a label insert or the like
associated with the subject test strips.
[0052] When a plurality of test strip devices is provided, they may
be collectively packaged within a cartridge, which may be reusable
or disposable. Certain of such kits may include various types of
test strip devices, (e.g., electrochemical and/or colorimetric test
strip devices). These various test strip devices may contain the
same or different reagents.
[0053] Regardless of the nature of the constituent components of
any systems according to the present invention, the subject test
strip devices, (whether electrochemical, calorimetric or
otherwise), are preferably configured and adapted to be inserted
into the meter. More specifically, as illustrated in FIG. 1, test
strip device 2 has a first end 8 and a second end 10, wherein the
skin-piercing or lancing blade or needle 4 is associated with first
end 8 and at least the second end 10 is configured for insertion
into meter 6.
[0054] Meter 6 preferably has an ergonomically-designed housing 12
having dimensions which allow it to be comfortably held and
manipulated with one hand. Housing 12 may be made of a metal,
plastic or other suitable material, preferably one that is light
weight but sufficiently durable. The distal portion 14 of the
housing provides an aperture 16 through which test strip device 2
is advanced from a retracted position within meter 6 to an extended
position wherein at least a portion of the test strip
microneedle/lancet 4 extends a distance outside aperture 16.
[0055] Distal portion 14 further defines a chamber in which test
strip device 2 is received within a test strip receiving mechanism
18. Test strip device 2 may be inserted into meter 6 by removing
distal housing portion 14 from housing 12 and inserting test strip
device 2 into test strip receiving mechanism 18. Alternatively,
test strip device 2 may be inserted into meter 6 and received into
mechanism 18 via aperture 14.
[0056] Preferably, distal housing portion 14 is transparent or
semi-transparent to allow the user to visually confirm proper
engagement between test strip device 2 and receiving area 18 prior
to conducting the analyte concentration assay, as well as to
visualize the test site and to visually confirm the filling of
strip 2 with body fluid during the assay (especially if electronic
sensing is not provided to discern the same). When test strip
device 2 is properly seated within receiving mechanism 18, the
biosensor with test strip device 2 operatively engages with the
meter's testing components. In the case of electrochemical test
strip embodiments, the electrodes of the biosensor operatively
engage with the meter's electronics; with calorimetric test strip
embodiments, the matrix or membrane area having a signal producing
system is operatively aligned with the meter's optical components.
The meter's electronics or optical componentry, upon sensing when
the reaction zone or matrix area, respectively, within test strip
device 2 is filled with the sampled fluid, supplies an input signal
to the test strip biosensor and receives an output signal therefrom
which is representative of the sample fluid characteristic being
measured.
[0057] Circumferentially positioned about aperture 16 is a pressure
ring 20, the distal surface of which is applied to the skin and
encircles the piercing site within the skin during a testing
procedure. The compressive pressure exerted on the skin by pressure
ring 20 facilitates the extraction of body fluids from the
surrounding tissue and the transfer of such fluid into test strip
device 2.
[0058] Distal housing portion 14 is preferably itself in movable
engagement with meter 6 wherein distal housing portion 14 is
slightly translatable or depressible along a longitudinal axis of
the meter. Between distal housing portion 14 and the a proximal
portion of housing 12, is a pressure sensor 22 which senses and
gauges the amount of pressure exerted on distal housing portion 14
when compressing pressure ring 20 against the skin. Pressure sensor
22 is preferably an electrical type sensor which may be of the kind
commonly known in the field of electronics. Pressure sensor
indicators 24, in electrical communication with pressure sensor 22,
are provided to indicate the level of pressure being applied to
distal housing portion 14 so that the user may adjust the amount of
pressure being applied, if necessary, in order to apply an optimal
pressure.
[0059] In many embodiments, meter 6 has a display 26, such as an
LCD display, for displaying data, such as input parameters and test
results. Additionally, meter 6 has various controls and buttons for
inputting data to the meter's processing components and for
controlling the piercing action of test strip device 2. For
example, lever 28 is used to retract test strip device 2 to a
loaded position within meter 6 and thereby pre-load a spring
mechanism (not shown) for later, on-demand extension or ejection of
test strip device 2 from aperture 16 by depressing button 30. When
distal housing portion 04 is properly positioned on the skin, such
ejection of test strip device 2 causes microneedle 4 to
instantaneously pierce the skin for accessing the body fluid
therein. Buttons 32 and 34, when depressed, input signals to the
meter's processing components indicating whether the measurement to
be made is for testing/information purposes (and for recovering the
test results from a memory means within the meter's electronics) or
for calibration purposes, respectively.
[0060] Meter 6 may further be configured to receive and retain a
replaceable cartridge containing a plurality of the subject test
strip devices. After using a test strip device, the meter may
either eject the used test strip from the meter or store them for
disposal at a later time. Such a configuration eliminates the
necessary handling of test strips, thereby minimizing the
likelihood of damage to the strip and inadvertent injury to the
patient. Furthermore, because manual handling of the test strips is
eliminated, the test strips may be made much smaller thereby
reducing the amount of materials required, providing a cost
savings. The meter disclosed in U.S. patent application Ser. No.
______, entitled "Minimal Procedure Analyte Test System," having
attorney docket no. LIFE-054 and filed on the same day herewith, is
of particular relevance in regard to these considerations.
[0061] Additionally, certain aspects of the functionality of meters
suitable for use with the subject systems are disclosed in U.S.
Pat. No. 6,193,873, as well as in co-pending, commonly owned U.S.
application Ser. Nos. 09/497,304, 09/497,269, 09/736,788,
09/746,116 and 09/923,093. Of course, in those embodiments using a
colorimetric assay system, a spectrophotometer or optical meter
will be employed, where certain aspects of the functionality of
such meters suitable for use are described in, for example, U.S.
Pat. Nos. 4,734,360, 4,900,666, 4,935,346, 5,059,394, 5,304,468,
5,306,623, 5,418,142, 5,426,032, 5,515,170, 5,526,120, 5,563,042,
5,620,863, 5,753,429, 5,773,452, 5,780,304, 5,789,255, 5,843,691,
5,846,486, 5,968,836 and 5,972,294.
[0062] In use, the subject invention provides methods for
determining a characteristic of the sample, e.g., the concentration
of an analyte in a sample. The subject methods find use in the
determination of a variety of different analyte concentrations,
where representative analytes include glucose, cholesterol,
lactate, alcohol, and the like. In many embodiments, the subject
methods are employed to determine the glucose concentration in a
physiological sample. Test devices 2 according to the present
invention are particularly suited for use in determining the
concentration of an analyte in blood or blood fractions, and more
particularly in whole blood or interstitial fluid.
[0063] In practicing the subject methods, at least one subject test
strip device as described above, is provided, and a subject
microneedle 4 thereof is inserted into a target area of skin.
Typically, the skin-piercing element is inserted into the skin of a
finger or forearm for about 1 to 60 seconds, usually for about 1 to
15 seconds and more usually for about 1 to 5 seconds. Depending on
the type of physiological sample to be obtained, the subject
skin-piercing element 4 may be penetrated to various skin layers,
including the dermis, epidermis and the stratum corneum, but in
many embodiments will penetrate no farther than the subcutaneous
layer of the skin.
[0064] While the subject test strips may be handled and inserted
into the skin manually, the subject test strips are preferably used
with a hand-held meter such as described above. As such, a single
test strip device 2 is either initially inserted into test strip
meter or the test strip may be provided by a pre-loaded cartridge
(not shown). In the latter approach embodiment, the cartridge is
preferably removably engageable with meter 6. Used strips may be
automatically disposed of, e.g., either ejected from the meter or
deposited into a separate compartment within the cartridge, while
an unused test strip is automatically removed from the cartridge
and inserted into a receiving area of the meter.
[0065] Once test strip device 2 is properly received within
mechanism 18, it may then be spring loaded or cocked by means of
lever 28, thereby retracting the test strip device 2 and preparing
it for firing. Meter 6 is then positioned substantially
perpendicular to the targeted skin surface wherein distal housing
portion 14, and more specifically pressure ring 20, is caused to
contact the target skin area. Some compressive pressure may be
manually applied to the target skin area, i.e., by pressing the
distal end of meter 14 against the target skin area, to ensure that
skin-piercing element 4 is properly inserted into the skin. By
applying such pressure, a counter force causes distal housing
portion 14 to press back upon pressure sensor 22.
[0066] The relative amount (i.e., high, normal and low) of counter
pressure is then measured and displayed by optional pressure sensor
indicators 24. Preferably, the amount of pressure applied should
generally be in the "normal" range. Indicators 24 inform the user
as to when too much or too little pressure is being applied. When
the indicators show that the applied pressure is "normal", the user
may then depress the spring-release button 30. Due to the spring
force released, receiving/carrying mechanism 18 and test strip
device 2 are caused to thrust forward thereby causing skin-piercing
element 4 to extend from aperture 16 and puncture the targeted skin
area.
[0067] Whether by manual means or by use of meter 6, the
penetration of skin-piercing element 4 into the skin may create a
fluid sample pooling area (defined by the recess or opening within
skin-piercing element variations shown in FIGS. 4A-7 and described
further therewith). In which case, sample fluid enters the pooling
area by the open-space configuration (e.g., recess or opening,
within skin piercing element 4), and possibly also from the
opposite side of the skin-piercing element. The pooled sample fluid
is then transferred directly to the reaction zone of a test strip
or thereto by a fluid pathway by at least a capillary force exerted
on the pooled fluid. Where no enlarged pooling area is provided, a
simple capillary channel may prove effective in certain situations
as well, though such a set-up may not be most preferred.
[0068] In any case, the transfer of fluid from the wound site to
the biosensor may be further facilitated by exerting physical
positive pressure circumferentially around the penetration site by
means of a pressure ring 20 or by applying a source of negative
pressure through the fluid channel thereby vacuuming the body fluid
exposed to the distal end of the channel. Fluid passing into the
biosensor reaction zone may simply fill the area or alternately be
distributed by subchannels or another similar distribution
feature.
[0069] Once meter 6 senses that the reaction zone or matrix area is
completely filled with the sample of body fluid, the meter
electronics or optics are activated to perform analysis of the
extracted sample. At this point, the meter may be removed by the
patient from the penetration site or kept on the skin surface until
the test results are shown on the display. Meter 6 may
alternatively or additionally include means for automatically
retracting the microneedle strip from the skin once the reaction
cell is filled with the body fluid sample.
[0070] With an electrochemical-based analyte concentration
determination assay, an electrochemical measurement is made using
the counter/reference and working electrodes. The electrochemical
measurement that is made may vary depending on the particular
nature of the assay and the meter with which the electrochemical
test strip is employed, (e.g., depending on whether the assay is
coulometric, amperometric or potentiometric). Generally, the
electrochemical measurement will measure charge (coulometric),
current (amperometric) or potential (potentiometric), usually over
a given period of time following sample introduction into the
reaction area. Methods for making the above described
electrochemical measurement are further described in U.S. Pat.
Nos.: 4,224,125; 4,545,382; and 5,266,179; as well as in
International Patent Publications WO 97/18465 and WO 99/49307.
[0071] Following detection of the electrochemical signal generated
in the reaction zone, the amount of the analyte present in the
sample is typically determined by relating the electrochemical
signal generated from a series of previously obtained control or
standard values. In many embodiments, the electrochemical signal
measurement steps and analyte concentration derivation steps, are
performed automatically by a device designed to work with the test
strip to produce a value of analyte concentration in a sample
applied to the test strip. A representative reading device for
automatically practicing these steps, such that user need only
apply sample to the reaction zone and then read the final analyte
concentration result from the device, is further described in
co-pending U.S. application Ser. No. 09/333,793 filed Jun. 15,
1999.
[0072] For a calorimetric or photometric analyte concentration
determination assay, sample applied to a subject test strip, more
specifically to a reaction area of a test strip, is allowed to
react with members of a signal producing system present in the
reaction zone to produce a detectable product that is
representative of the analyte of interest in an amount proportional
to the initial amount of analyte present in the sample. The amount
of detectable product (i.e., signal produced by the signal
producing system) is then determined and related to the amount of
analyte in the initial sample. With such colorimetric assays,
optical-type meters are used to perform the above mentioned
detection and relation steps. The above described reaction,
detection and relating steps, as well as instruments for performing
the same, are further described in U.S. Pat. Nos. 4,734,360;
4,900,666; 4,935,346; 5,059,394; 5,304,468; 5,306,623; 5,418,142;
5,426,032; 5,515,170; 5,526,120; 5,563,042; 5,620,863; 5,753,429;
5,773,452; 5,780,304; 5,789,255; 5,843,691; 5,846,486; 5,968,836
and 5,972,294; the disclosures of which are herein incorporated by
reference. Examples of such colorimetric or photometric reagent
test strips suitable for use with the subject invention include
those described in U.S. Pat. Nos.: 5,563,042; 5,753,452; 5,789,255,
herein incorporated by reference.
[0073] Test Strip Devices
[0074] Turning now to FIGS. 2A and 2B, a first test element or
tester 2 is shown. It comprises a test strip 36 and a
needle/microneedle or lance/lancet portion 38 (herein used
interchangeably). FIG. 2B shows the lance element 38 shown
separately, whereas a discrete test strip 36 and lance element 38
and are affixed, held or attached to each other in FIG. 2A to form
tester 2
[0075] The test strip includes a biosensor 40 set upon a substrate
42. Adhesive member(s) 44 may be provided to make the connection.
The biosensor shown in FIG. 2A is a colorimetric-type sensor
provided in connection with a membrane and/or matrix. An aperture
or transparent window 46 may be provided in substrate 42 to enable
sensor reading.
[0076] To attach the lance element in FIG. 2B to the test strip in
FIG. 2A adhesive member(s) 48 are applied to a base 50 of the lance
element to connect it to an opposing portion of the test strip. The
orientation of such members may, of course, vary. Generally they
will be set so as not to interfere with relevant structure. FIGS.
5A and 5B provide an example of alternate adhesive portion
placement used to attach the lance element to a test strip.
[0077] Regardless of relative orientation or configuration, as with
optional adhesive portions 44, adhesive portions 48 may comprise
double-stick tape or directly-applied adhesive. Alternately,
adhesive affixation of elements 36 and 38 may be foregone in favor
of mechanically welding (for instance, using ultrasonics) or
chemically welding the components together. Still further,
supplemental attachment members may be provided to connect a test
strip with a lance element according to the present invention.
[0078] An example of such an approach is shown in FIGS. 3A and 3B.
Here, lance member 38 includes hooks or clasp members 52 provided
on opposites sides of base 50. The clips may be integrally formed
in the lance element as shown, or comprise independent or discrete
members themselves.
[0079] The variations of the invention in FIGS. 4A and 4B are shown
using adhered-on lance members 38 on their respective undersides.
The base of each lance member may be affixed to the test strip body
36 by an adhesive layer or layers 44. Of course clip-on lance
members may alternately be used as may be other methods of
connection.
[0080] As shown, the lance member in FIG. 4A is of a different
thickness than that in FIG. 4B. This is because the former is sized
to be made from plastic, while it is contemplated that the latter
be produced from a metal. Indeed, any of the various lance member
variations shown may alternately be made of either metal, plastic,
composite material, ceramic or another material and be configured
accordingly. Likewise, as may already be apparent, any of the
attachment approaches described may be use in or with any of the
lance member variations.
[0081] Still further, each of the optional features regarding
needle 4 structure and fluid conveyance as described further below
may be used in each of the variations with either type of test
strip 36 disclosed and still others.
[0082] However, details of the test strip embodiment in FIGS. 4A
and 4B is first described. Specifically, this test strip 36
comprises a first electrode 54 and a second electrode 56,
preferably constructed as described above in connection with
electrochemical sensor production. The thickness of the any
substrate material provided typically ranges from about 25 to 500
.mu.m and usually from about 50 to 400 .mu.m, while the thickness
of the metal layer typically ranges from about 10 to 100 nm and
usually from about 10 to 50 nm.
[0083] An adhesive member 58 may serve as a spacer between the
electrodes, defining a reaction zone or area 60 for which the
electrodes generally face each other and are separated by only a
short distance, such that the spacing between the electrodes is
extremely narrow. The thickness of spacer layer 58 may range from
10 to 750 .mu.m and is often less than or equal to 500 .mu.m, and
usually ranges from about 25 to 175 .mu.m. Any spacer layer
preferably has double-sided adhesive to capture the adjacent
electrodes. In any case spacer layer 58 may be fabricated from any
convenient material, where representative suitable materials
include polyethylene terephthalate, glycol modified polyethylene
terephthalate (PETG), polyimide, polycarbonate, and the like.
[0084] As depicted, the working and reference electrodes are
generally configured in the form of strips. Typically, the length
of the electrodes ranges from about 0.75 to 2 in (1.9 to 5.1 cm),
usually from about 0.79 to 1.1 in (2.0 to 2.8 cm). The width of the
electrodes ranges from about 0.15 to 0.30 in (0.38 to 0.76 cm),
usually from about 0.20 to 0.27 in (0.51 to 0.67 cm). In certain
embodiments, the length of one of the electrodes is shorter than
the other, wherein in certain embodiments it is about 0.135 in (3.5
mm) shorter. Preferably, electrode and spacer width is matched
where the elements overlap. The spacer incorporated in the strip
may be set back about 0.3 in (7.6 mm) from the end of electrode 56,
leaving opening(s) 62 between the electrodes about 0.165 in (4.2
mm) deep. However, configured, such opening(s) provide space for
receipt of a meter probe.
[0085] A vent opening 64 is provided across the reaction zone from
the inlet port 66. Providing a vent allows for capillary action
between the electrodes to draw sample into the reaction zone
without backpressure interference. Spacer layer 58 is preferably
configured or cut-out so as to provide a reaction zone or area with
a volume in the range from about 0.01 to 10 .mu.L, usually from
about 0.1 to 1.0 .mu.L and more usually from about 0.05 to 1.0
.mu.L. The amount of physiological sample that is introduced into
the reaction area of the test strip may vary, but generally ranges
from about 0.1 to 10 .mu.l, usually from about 0.3 to 0.6
.mu.l.
[0086] Such introduction of sample is preferably accomplished at
notched section 68. It interfaces with features of needle 4 to pick
up pooling or conveyed sample and direct it inwardly toward the
test strip reaction zone, at least partially pinning the sample
along the edges of the notch.
[0087] As such, the variations of the invention shown in FIGS. 4A
and 4B represent front-loaded test strips. Those in FIGS. 2A and 2B
are loaded with or accept sample along the face of the sensor (as
present on the underside of the test strip). Still further modes of
introduction are possible, however. Side loaded test strips may be
employed (such as those described in the above-referenced patent
application Attorney Docket Nos. LIFE-031/LIFE-039 with minor
modifications of the lance elements depicted. Such approaches are
contemplated as part of the present invention.
[0088] Lance Elements
[0089] Also contemplated as aspects of the present invention are
various features regarding the lance elements 38 shown. In
accordance with the text above, each lance element includes a
lancet/needle or skin piercing element 4, typically having a
pointed tip 70. In addition the body of lance 4 and base 50 may
incorporate various features to collect and/or convey a biological
sample to a given test strip sensor 40.
[0090] Actually, any suitable shape of skin-piercing element 4 may
be employed with the subject test strip devices, as long as the
shape enables the skin to be pierced with minimal pain to the
patient. For example, the skin-piercing element may have a
substantially flat or planar configuration, or may be substantially
cylindrical-like, wedge-like or triangular in shape such as a
substantially flattened triangle-like configuration, blade-shaped,
or have any other suitable shape. The cross-sectional shape of the
skin-piercing element, or at least the portion of skin-piercing
element that is penetrable into the skin, may be any suitable
shape, including, but not limited to, substantially rectangular,
oblong, square, oval, circular, diamond, triangular, star, etc.
Additionally, the skin-piercing element may be tapered or may
otherwise define a point or apex at its distal end. Such a
configuration may take the form of an oblique angle at the tip or a
pyramid or triangular shape or the like.
[0091] The dimensions of the skin-piercing element may vary
depending on a variety of factors such as the type of physiological
sample to be obtained, the desired penetration depth and the
thickness of the skin layers of the particular patient being
tested. Generally, the skin-piercing element is constructed to
provide skin-piercing and fluid extraction functions and, thus, is
designed to be sufficiently robust to withstand insertion into and
withdrawal from the skin. Typically, to accomplish these goals, the
ratio of the penetration length (defined by the distance between
the base of the skin-piercing element and its distal tip) to
diameter (where such diameter is measured at the base of the
skin-piercing element) is from about 1 to 1, usually about 2 to 1,
more usually about 5 to 1 or 10 to 1 and oftentimes 50 to 1.
[0092] The total length of the skin-piercing elements generally
ranges from about 1 to 30,000 microns, usually from about 100 to
10,000 microns and more usually from about 1,000 to 3,000 microns.
The penetration length of the skin-piercing elements generally
ranges from about 1 to 5000 microns, usually about 100 to 3000
microns and more usually about 1000 to 2000 microns. The height or
thickness of skin-piercing elements 38, at least the thickness of
the distal portion 4, typically ranges from about 1 to 1000
microns, usually from about 10 to 500 microns and more usually from
about 50 to 250 microns. The outer diameter at the base generally
ranges from about 1 to 2000 microns, usually about 300 to 1000
microns and more usually from about 500 to 1000 microns. In many
embodiments, the outer diameter of the distal tip generally does
not exceed about 100 microns and is generally less than about 20
microns and more typically less than about 1 micron. However, it
will be appreciated by one of skill in the art that the outer
diameter of the skin-piercing element may vary along its length or
may be substantially constant.
[0093] Regarding the fluid-conveying features noted as may be
incorporated in lance element 38, one variation incorporates only a
channel 72, preferably of capillary dimensions, for this purpose.
Configured to work with the test strips in FIGS. 2A and 3A, the
channel preferably extends a sufficient length so that it is in
fluid communication with the sensor matrix or membrane. The channel
may be open on either one side (thereby taking the form of a
trench) or both. The channel length is preferably limited to
match-up with intended target in order to avoid inadvertent loss of
sample fluid.
[0094] FIGS. 4A and 4B show a somewhat different lance
configuration. In each figure, a recessed polling area 74 is
provided. No capillary is required to carry fluid from the pooling
area since (as noted above) fluid is able to directly transfer from
the lancet 4 to access port 66 in this variation of the invention.
The purpose of the recessed or space-defining area in the
variations shown in FIGS. 4A and 4B (as well as in FIGS. 5A-7) is
to create a space or volume within the pierced tissue. This space
serves as a reservoir within which bodily fluid is caused to pool
in situ prior to being transferred to the biosensor portion of the
subject test strip devices. As such, the availability of a greater
volume of body fluid can be provided with a tip that is smaller
and/or sharper than conventional microneedles, thereby reducing
pain. The greater availability of body fluid also results in a
faster collection rate of sampling.
[0095] Generally, the space-defining lancet configurations of the
present invention create or define a space within the pierced
tissue having a volume at least as great as the available fluid
volume in the reaction zone of the biosensor. Such space or volume
ranges from about 10 to 1,000 nL, and more usually from about 50 to
250 nL. Such volume occupies a substantial portion of the entire
volume occupied by the structure of the skin-piercing element, and
ranges from about 50% to 99% and more usually from about 50% to 75%
of the entire volume occupied by the skin piercing element.
[0096] The lance member variations shown in FIGS. 5A-7 incorporate
a channel 72 and a recess 74. The variations in FIGS. 5 and 6
include an opening 76 adjacent the pooling region as well. The
pooling area opening in the former variations is best pictured in
FIG. 5B. The purpose of such an opening (and for providing an open
capillary in the lance member variations referenced above from
FIGS. 2A-3B) is to further expose the sample-gathering structure
area to the outside environment, thereby increasing the volume and
flow rate of body fluid into the area.
[0097] As illustrated, the recesses and/or openings may occupy a
substantial portion of the width of their respective skin-piercing
elements, as well as a substantial portion of a length dimension.
Side walls 78 defining each of the structures will have a thickness
sufficient to maintain the structure of the microneedle when
subject to normal forces, but may be minimized in order to maximize
negative space for collecting sample.
[0098] Another optional feature or set of features that may be
employed, especially in connection with a fluid conveying channel
72 incorporated in a lance element is shown in each of FIGS. 5A-7.
The features being referred to are the secondary fluid transfer
pathways 80. These elements, set in fluid communication with
channel 72 convey sample outwardly, dispersing the same across the
sensor employed in an opposing, attached test strip.
[0099] Like channel 72, pathways or channels 80 are preferably
dimensioned so as to exert a capillary force on fluid within the
pooling area defined by the open space portion of the microneedle,
and draws or wicks physiological sample to within the reaction zone
or matrix area of the biosensor. As such, the diameter or width of
a single fluid channel or pathway does not exceed 1000 microns and
will usually be about 100 to 200 microns in diameter. This diameter
may be constant along its length or may vary. It may be preferred
that sub-channels 80 have cross-sectional diameters in the range
from about 1 to 200 microns and more usually from about 20 to 50
microns in that they are not required to convey the same volume of
fluid as a primary channel 72.
[0100] In the illustrated embodiments, branch channels 80 extend
perpendicularly from channel 72; however, they may extend angularly
from their respective channels. Another variation concerning lance
member configuration relative to channels 80 is to inset or
surround the same within base as shown in FIG. 7. Accomplished in
this manner or another way, bounding the area to which channels 80
can convey fluid can be employed to ensure that sample is directed
fully and only to a reaction or sensor area of the test strip 36
employed with lance element 38.
[0101] In certain embodiments of the invention, the fluid pathway
may further include one or more agents to facilitate sample
collection. For example, one or more hydrophilic agents may be
present in the fluid pathway, where such agents include, but are
not limited to types of surface modifiers or surfactants such as
mercaptoethane sulfonic acid (MESA), Triton, Macol, Tetronic,
Silwet, Zonyl, Aerosol, Geropon, Chaps, and Pluronic.
[0102] Test Strip Device Fabrication
[0103] Many of the techniques described in U.S. Application Atty
Docket No. LIFE-035 entitled "PHYSIOLOGICAL SAMPLE COLLECTION
DEVICES AND METHODS OF USING THE SAME" are applicable to
fabricating test strip devices as described herein--especially
those details regarding needle/lance production. Details as to
electrochemical test strip production may also be appreciated in
view of Application Atty Docket Nos. LIFE-031 entitled "SOLUTION
DRYING SYSTEM" and LIFE-039 entitled "SOLUTION STRIPING
SYSTEM".
[0104] A primary distinction, however, between the approach taught
in the former application and that taught herein, is that in the
present invention complete test strips may be provided, to which
lance elements are attached as auxiliary structure. FIGS. 2A and 3A
provide examples of such an approach. Alternately, test strips
adapted for use with the lance elements of the invention may be
provided, to which lance elements are affixed. FIGS. 4A and 4B
provide examples of such an approach.
[0105] In either case, it is possible to separately produce or
procure lance and test strip elements that are later brought
together. The initially independent nature of the products/devices
permits relatively optimized manufacture. In contrast, in the
integral test strip devices described in the above-referenced
application, certain considerations of material selection and
manufacturing processes applicability that do not necessarily
affect manufacture of the present invention.
[0106] One example of the flexibility offered by producing test
strip devices according to the present invention by affixing a
lance element to an otherwise complete test strip is that a user
may feasibly take such action. This may be especially true for the
clip-type embodiments disclosed (or variations of the embodiments
shown in which clip-type structure may be employed.) By virtue of
such flexibility, there is market opportunity for selling lance
members for use with any of a variety of commercially available
test strips to be used with a meter according to the present
invention. Of course, flexibility exists in designing the lance
elements so they will interface (by clips, adhesive or other means)
with a wide variety of test strips--both, present and future.
CLAIMS
[0107] Though the invention has been described in reference to
certain examples, optionally incorporating various features, the
invention is not to be limited to the set-ups described. The
invention is not limited to the uses noted or by way of the
exemplary description provided herein. It is to be understood that
the breadth of the present invention is to be limited only by the
literal or equitable scope of the following claims. That being
said, we claim:
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